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Hepatitis C Virus NS5A and Core protein induce hepatic stellate cells activation promoting fibrosis-related gene regulation on hepatocytes.
Tania G. Heredia-Torres1, Sonia A. Lozano-Sepúlveda1, Ana R. Rincón-Sánchez2, Ana M. Guadalupe Rivas-Estilla1
1 Departamento de Bioquímica y Medicina Molecular, Centro de Investigación e Innovación en Virología MédicaFacultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
2 IBMMTG, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="para0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Ethical statement</span></p><p id="para0006" class="elsevierStylePara elsevierViewall">The protocol was registered and approved by the Ethics Committee&#46;</p><p id="para0007" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Declaration of interests</span></p><p id="para0008" class="elsevierStylePara elsevierViewall">None</p><p id="para0009" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Funding</span></p><p id="para0010" class="elsevierStylePara elsevierViewall">The study was funded by the Department of Biochemistry and Molecular Medicine and CIIViM&#44; School of Medicine&#44; and by PAICYT 171-CS-2022 from Universidad Aut&#243;noma de Nuevo Le&#243;n &#40;UANL&#41;&#44; Monterrey&#44; Nuevo Le&#243;n 64460&#44; Mexico&#46;</p></span>"
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        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0001">Introduction and Objectives</span><p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Chronic HCV infection leads to the development of liver fibrosis mediated by intercellular communication between hepatocytes and hepatic stellate cells &#40;HSCs&#41;&#46; The diverse molecular pathways involved in the development of fibrosis in hepatocytes derived from HSC activation induced by viral proteins remain to be fully determined&#46; Our aim is to determine differentially expressed genes associated with fibrotic processes in hepatocytes &#40;Huh7&#41; that express the HCV NS5A or Core protein during co-culture with HSC &#40;LX2&#41;&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Materials and methods</span><p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Huh7 cells were transfected to express NS5A or Core proteins and co-cultured with HSC-LX2 cells&#46; Viral protein expression and expression of TGF&#946;1&#44; Col1&#44; and aSMA was determined to assess LX2 activation&#46; A profile of 84 genes associated with fibrosis during co-cultivation was determined and analyzed&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Results</span><p id="spara003" class="elsevierStyleSimplePara elsevierViewall">HSC-LX2 co-cultured with transfected Huh7 showed an 8&#46;3&#44; 6&#46;7 and 4-fold increase in collagen1&#44; TGFB1 and timp1 expression respectively induced by NS5A and a 6&#46;5&#44; 1&#46;8 and 6&#46;2-fold increase respectively induced by Core&#44; all these compared to HSC-LX2 co-cultured with untransfected Huh7&#46; We detected 28 overexpressed genes in Huh7 &#40;NS5A&#43;&#41; and 46 differentially expressed genes in Huh7 &#40;Core&#43;&#41; in co-culture with HSC-LX2&#44; compared to untransfected Huh7 in co-culture with HSC-LX2&#46; Analysis of the expression profile showed that the TGF&#946;1&#44; the ECM regulation&#44; and growth factors pathways are the molecular mechanisms involved during the co-culture of Huh7 transfected with NS5A or Core with HSC-LX2&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Conclusions</span><p id="spara004" class="elsevierStyleSimplePara elsevierViewall">HCV NS5A and Core proteins expression in Huh7 cells induces the HSC-LX2 activation&#44; regulating the expression of diverse genes in hepatocytes that trigger different molecular mechanisms involved in the fibrosis development&#44; this information provide the identification of possible anti-fibrotic targets drugs associated with HCV infection for further study&#46;</p></span>"
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Article information
ISSN: 16652681
Original language: English
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